Among rare cases of teratozoospermia, MMAF (multiple morphological abnormalities of the flagellum) syndrome is a complex genetic disorder involving at least 70 different genes. As the name suggests, patients with MMAF syndrome produce spermatozoa with multiple flagellar defects, rendering them immobile and non-fertilizing, leading to complete infertility in affected men. The only viable treatment option is ICSI. What is less understood is the presence of the various types of head defects in the spermatozoa, which are consistently present. Due to the involvement of numerous genes and the limited number of patients with MMAF syndrome, research on head defects and their impact on embryonic development remains insufficiently explored. To address these questions, a comparative study was conducted under controlled experimental conditions using four knockout (KO) mouse lines targeting Cfap43, Cfap44, Armc2, and Ccdc146 genes, all associated with MMAF syndrome in humans and mice. Each KO line underwent a detailed examination of nuclear defects, including morphology, DNA compaction, chromosomal architecture, and ploidy. The study revealed significant heterogeneity among the four lineages, with the extent of defects varying depending on the lineage, ranked as Ccdc146-/- > Cfap43-/- > Armc2-/- ≈ Cfap44-/-. The developmental potential of sperm from males in each lineage was assessed by injecting them into wild-type oocytes, and embryo development was monitored up to the blastocyst stage. Sperm from all KO lines exhibited a marked decrease in supporting embryo development compared to the wild-type, with developmental failure rates ranked as follows: Ccdc146 > Cfap43 > Armc2 > Cfap44-deficient sperm. The degree of developmental failure thus correlated with the severity of nuclear defects, and zygotes produced with sperm from Ccdc146-/- and Cfap43-/- mice showed the highest rates of developmental impairment. These findings from preclinical models highlight the heterogeneous nature of MMAF syndrome, both in terms of sperm nuclear defects and developmental potentials. Genetic characterization in humans is therefore crucial for improving therapeutic counselling in affected individuals.